A formulation of self-assembled peptido-nanomicelles has been developed for a combinational treatment of SDT, PDT and chemotherapy to nasopharyngeal carcinoma. In vitro cellular tests and in vivo mice therapy proved effective for targeted tumor growth inhibition. These merits provided a novel approach to non-invasive cancer treatments.

SRY-related high-mobility-group box 9 (SOX9) is a member of the SOX family of transcription factors. Accumulating evidence has shown that SOX9 plays a significant role in various malignancies. However, the role of SOX9 in nasopharyngeal carcinoma (NPC) remains unknown. In the present study, up-regulation of SOX9 was observed in both NPC tissues and different NPC cells. Overexpression of SOX9 promoted NPC cell proliferation, migration and invasion. Conversely, knock down of SOX9 inhibited NPC proliferation, colony formation, migration and invasion. Mechanistically, SOX9 bound directly to the promoter region of BMP2 and increased BMP2 expression. In addition, overexpression of SOX9 activated the mTOR pathway partly through BMP2. Collectively, these results identify a novel role for SOX9 as a potential therapeutic marker for the prevention and treatment of NPC.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an EBV-associated neoplasm occurring endemically in Southeast Asia and sporadically all over the world. In children and adolescents, high cure rates have been obtained using chemotherapy, radiochemotherapy and maintenance therapy with interferon beta (IFNβ). The mechanism by which IFNβ contributes to a low systemic relapse rate has not yet been fully revealed.
PATIENTS AND METHODS: NK cells and serum samples from two patients with NPC were analyzed before and at different time points during IFNβ therapy, for assessment of TRAIL expression and NK cell cytotoxicity. Cytotoxicity was measured using the calcein release assay and the contribution of different death effector pathways was analyzed using specific inhibitors.
RESULTS: Treatment with IFNβ induced TRAIL expression on patients' NK cells and increased their cytotoxicity against NPC targets in vitro. NK cell-mediated cytotoxicity was predominately mediated via TRAIL. IFNβ also induced the production of soluble TRAIL (sTRAIL) by NK cells and its release upon contact with NPC cells. IFNβ treatment increased serum levels of sTRAIL in patients. Moreover, sTRAIL concentrated from patients' serum samples induced apoptosis ex vivo in NPC cells from a patient-derived xenograft.
CONCLUSION: Increased cytotoxicity of NK cells against NPC cells and increased serum levels of biologically active TRAIL in patients treated with IFNβ could be a means to eliminate micrometastatic disease and explain the low systemic relapse rate in this patient group.

For patients with nasopharyngeal carcinoma (NPC), prognostic indicators to customize subsequent biologically conformal radiation therapy may be obtained via 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT). This retrospective study assessed the prognostic significance and feasibility of conformal radiotherapy for NPC, based on F-FDG PET/CT. Eighty-two patients with NPC underwent F-FDG PET/CT prior to intensity-modulated radiation therapy (IMRT). The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the primary tumor were measured, with MTVx based on absolute SUVx values ≥ specific threshold x on each axial image. The cut-off SUVmax and MTV values for predicting 3-year progression-free survival (PFS) were calculated according to a receiver operating characteristic curve. Assessed were correlations between SUVmax and MTV and between threshold x and MTVx, and the MTV percentage of the primary tumor volume at threshold x. The SUVmax and MTV were positively associated, as were MTV and primary tumor volume. Primary tumor volume, SUVmax, and MTV were significant predictors of survival. The 3-year PFS rates for SUVmax ≤8.20 and >8.20 were 91.1% and 73.0%, respectively (P = .027). With furthermore analysis, patients having tumor with smaller MTV had higher 3-year PFS than patients having tumor with larger MTV. The 3-year PFS rate was inversely related to MTV. SUVmax and MTV, derived by PET/CT, are important for assessing prognosis and planning radiotherapy for patients with NPC. Small MTV indicated better 3-year PFS compared with large MTV. For the best therapeutic effect, MTV4.0 was the best subvolume to determine radiotherapy boost.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Asia particularly southern China. Comparisons of outcomes of conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) have been still debated. This meta-analysis was carried out to compare oncologic outcomes of CRT and IMRT in the treatment of NPC.
METHODS: A literature search was performed through PubMed, Embase, and the Cochrane library databases from their inceptions to November 10, 2018. Two authors assessed the included studies and extracted data independently. Relative studies that compared oncologic outcomes between CRT and IMRT for NPC were included.
RESULTS: A total of 13 eligible studies were included, which contained 1 RCT, 1 prospective study, and 11 retrospective studies. Our meta-analysis showed that IMRT has increased overall survival (OR = 0.51, 95% CI = 0.41-0.65, P < .00001), locoregional control rate (OR = 0.59, 95% CI = 0.52-0.67, P < .00001), disease-free survival (OR = 0.77, 95% CI = 0.65-0.91, P = .002), and metastasis-free survival (OR = 0.71, 95% CI = 0.54-0.94, P = .01) in comparison with CRT.
CONCLUSION: The results of this meta-analysis indicate IMRT should be a better option for the treatment of NPC because patients who underwent IMRT may benefit from increased overall survival, locoregional control rate, disease-free survival, and metastasis-free survival compared with CRT.

Nasopharyngeal carcinoma is characterised by distinct geographical distribution and is particularly prevalent in east and southeast Asia. Epidemiological trends in the past decade have shown that its incidence has declined gradually but progressively, and mortality has been reduced substantially. These findings probably reflect lifestyle and environmental changes, enhanced understanding of the pathogenesis and risk factors, population screening, advancements in imaging techniques, and individualised comprehensive chemoradiotherapy strategies. In particular, plasma Epstein-Barr virus (EBV) DNA has been used for population screening, prognostication, predicting treatment response for therapeutic adaptation, and disease surveillance. Moreover, the widespread application of intensity-modulated radiotherapy and optimisation of chemotherapy strategies (induction, concurrent, adjuvant) have contributed to improved survival with reduced toxicities. Among the existing developments in novel therapeutics, immune checkpoint therapies have achieved breakthroughs for treating recurrent or metastatic disease and represent a promising future direction in nasopharyngeal carcinoma.

Epithelial-mesenchymal transition (EMT) symbolizes the predominant program of advanced-stage cancer, it is critical in cancer progression, metastasis, and chemotherapy resistance. In this study, the metastatic properties of nasopharyngeal carcinoma (NPC) cells were evaluated by morphological examination, wound healing assay, migration and invasion assay. Western blotting and qRT-PCR were used to ascertain the expression of markers which were associated with EMT. The effects of miR-205-5p on invasion, migration, EMT and proliferation of NPC cells were evaluated and the molecular mechanisms of their interaction were explored. In this study, we manifested firstly that the expression of miR-205-5p in cisplatin-resistant NPC cell line HNE1/DDP was obviously up-regulated than that in its parental cell line HNE1. Then we analyzed the specific role of miR-205-5p through functional assays by transfecting specific mimics and inhibitors. The results indicated that low expression of miR-205-5p restrained EMT progression of HNE1/DDP cells. Further studies on the mechanism of miR-205-5p manifested that PTEN was a downstream candidate gene of miR-205-5p, down-regulated PTEN expression could counteract the effect of miR-205-5p inhibitors, and the regulation of EMT by miR-205-5p on HNE1/DDP cells depended on the PI3K/AKT signaling pathway. Overall, our results indicated that miR-205-5p was targeting PTEN to regulate EMT through the PI3K/AKT pathway. This study will supply a new treatment target for advanced NPC.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) protein is a member of the nucleotide excision repair (NER) system, which plays an important role in DNA damage repair. Recently, its predictive and prognostic value in nasopharyngeal carcinoma (NPC) has been investigated by several studies. However, their results remain controversial.
OBJECTIVES: In an attempt to address this issue, we conducted the present comprehensive meta-analysis.
DATA SOURCES: Studies published until November 2017 were searched. Finally, total 21 literatures involving 22 cohorts and 2921 NPC patients fulfilled the inclusion criteria.
RESULTS: The pooled results showed that high/positive expression of ERCC1 predicted poor objective response rate (ORR) [odds ratio (OR) = 2.83; 95% confidence interval (CI) = 2.11-3.80; P <.001], overall survival (OS) [hazard ratio (HR) = 1.77; 95% CI = 1.48-2.12; P <.001], and disease-free survival (DFS) (HR = 1.60; 95% CI = 1.43-1.79; P <.001) in NPC. Low heterogeneity was detected among these studies (ORR: I = 0.0%, P = .776; DFS: I = 38.7%, P = .148; OS: I = 0.0%; P = .530). The results of sensitivity analyses and publication bias verified the reliability of our findings.
CONCLUSIONS: This study suggested ERCC1 as a potential predictive and prognostic biomarker for the treatment response and survival prognosis of NPC patients.

OBJECTIVES: The aim of this review was to systematically evaluate the diagnostic accuracy of Raman spectroscopy (RS) in the identification of nasopharyngeal carcinomas from normal nasopharyngeal tissue.
METHODS: We searched six databases (PubMed, Embase, Cochrane Library, Web of Science, Scopus and CNKI) up to September 2018 for all published studies that assessed the diagnostic accuracy of RS in the detection of nasopharyngeal carcinomas. Non-qualifying studies were screened out in accordance with the specified exclusion criteria and relevant information about the diagnostic performance of RS extracted. A random effects model was adopted to calculate the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic threshold and diagnostic odds ratio (DOR). Additionally, we conducted a summary receiver-operating characteristic (SROC) curve analysis and threshold analysis, reporting area under the curve (AUC) to evaluate the overall performance of RS.
RESULTS: Three studies examined RS analysis in vivo, the pooled sensitivity and specificity of RS of which were 0.90 and 0.91, respectively, with an AUC of 0.9617. Eighteen studies assessed ex vivo samples, for which RS exhibited particularly high accuracy for the analysis of blood plasma.
CONCLUSIONS: RS was demonstrated to be a reliable technique for the detection of nasopharyngeal carcinoma with high accuracy, but additional studies are required to improve its performance and expand its application in ex vivo detection.

Aberrant expression of miR-31-5p has been detected in various cancers and plays a significant role in tumourigenesis. Low miR-31-5p expression was present in nasopharyngeal carcinoma (NPC) tissues and cell lines and acted as a tumour suppressive miRNA. Currently, circulating miRNAs are emerging as novel biomarkers for the early diagnosis of cancers using a non-invasive method. However, circulating miR-31-5p has rarely been reported in NPC. Therefore, the aim of this study was to explore peripheral blood miR-31-5p levels as a noninvasive biomarker and evaluate its clinical value for the early diagnosis of patients with NPC. A total of 110 participants were recruited, including 55 NPC patients and 55 healthy controls. Peripheral blood samples were collected from these participants, and total RNA was extracted to quantify the relative expression of miR-31-5p by RT-qPCR. We found a significantly lower expression of miR-31-5p in the NPC patients than in the healthy controls. Furthermore, low expression of miR-31-5p was highly correlated with tumor-node-metastasis (TNM) stage (I+II vs III+IV, p=0.001), T classification (T1 vs T2+T3+T4，p=0.036) and local lymph node metastasis (N1-N3 vs N0, p=0.002), but not distant metastasis (p=0.288). Moreover, miR-31-5p showed a moderate diagnostic performance (AUC=0.866, sensitivity=0.782, specificity=0.818). Thus, we concluded that circulating miR-31-5p can be a potentially novel and non-invasive biomarker for the early diagnosis of NPC and an attractive therapeutic target in NPC patients.

BACKGROUND: To evaluate the value of concurrent chemotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT), we performed this retrospective cohort study to compare the efficiency and toxicities of induction chemotherapy plus IMRT alone (IC + RT) versus induction chemotherapy plus IMRT-based concurrent chemoradiotherapy (IC + CCRT).
METHOD: We analyzed data from patients with locoregionally advanced NPC (stage III-IVb) who were treated at the West China hospital between January 2008 and December 2014. Patients received docetaxel, cisplatin, and 5-fluorouracil (TPF) IC followed by IMRT alone (IC + RT group) or IMRT plus cisplatin concurrent chemotherapy (IC + CCRT group). The main endpoint was overall survival (OS), which was evaluated by the Kaplan-Meier method and log-rank test. Multivariate Cox proportional hazard analysis was used to identify potential independent prognostic factors. Treatment-associated toxicities were compared between groups using the Chi squared test.
RESULTS: A total of 78 patients treated with IC + RT and 76 with IC + CCRT were analyzed. The median follow-up time was 59 months (range: 7-108 months). There was no difference between patients treated with IC + RT and IC + CCRT in terms of 3-year OS (89.0% versus 88.0%, p = 0.286), progression-free survival (76.8% versus 80.0%, p = 0.142), locoregional recurrence-free survival (87.1% versus 90.5%, p = 0.156), or distant metastasis-free survival (83.6% versus 82.6%, p = 0.567). Treatment (IC + RT versus IC + CCRT) was not an independent prognostic factor for OS (HR 1.425, 95% CI 0.698-2.908; p = 0.331). IC + CCRT was associated with a higher incidence of grade 3-4 neutropenia than IC + RT during radiotherapy (11.8% versus 1.3%, p = 0.020).
CONCLUSION: IC plus IMRT alone achieves similar patient survival outcomes as IC plus IMRT-based concurrent chemoradiotherapy, and has a lower incidence of toxicity.

Baicalein, an active ingredient separated from

BACKGROUND: Developing resistance to chemotherapeutic drugs has become a major problem in the management of nasopharyngeal carcinoma (NPC). To overcome this issue, use of natural plant products as chemosensitizers is gaining importance at a fast pace.
HYPOTHESIS/PURPOSE: The present study was designed to evaluate the cytotoxic effect and mode of action of a natural pentacyclic triterpenoid, celastrol, on cisplatin-resistant NPC cells.
RESULTS: Study results revealed that celastrol treatment significantly reduced the viability of NPC cells in dose and time dependent manners, as compared to untreated control cells. The cytotoxic effect of celastrol was mediated by cell cycle arrest at G2/M phase and induction of intrinsic and extrinsic apoptotic pathways. With further analysis, we observed that celastrol-induced activation of caspases was accompanied by increased phosphorylation of MAPK pathway proteins, p38, ERK1/2.
CONCLUSION: Taken together, our observation provides a novel insight on use of a natural plant product, celastrol, in the management of chemoresistant NPC.

Licochalcone A is widely studied in different fields and possesses antiasthmatic, antibacterial, anti-inflammatory, antioxidative, and anticancer properties. Its antimalignancy activity on renal, liver, lung, and oral cancer has been explored. However, limited studies have been conducted on the inhibitory effects of licochalcone A in human nasopharyngeal carcinoma cells. We determined cell viability using MTT assay. Cell cycle distribution and apoptotic cell death were measured via flow cytometry. Caspase activation and mitogen-activated protein kinase-related proteins in nasopharyngeal cancer cells in response to licochalcone A were identified by Western blot analysis. Results indicated that licochalcone A reduces cell viability and induces apoptosis, as evidenced by the upregulation of caspase-8 and caspase-9, caspase-3 activation, and cleaved-poly ADP-ribose polymerase expression. Treatment with licochalcone A significantly increases ERK1/2, p38, and JNK1/2 activation. Co-administration of a JNK inhibitor (JNK-IN-8) or p38 inhibitor (SB203580) abolishes the activation of caspase-9, caspase-8, and caspase-3 protein expression during licochalcone A treatment. These findings indicate that licochalcone A exerts a cytostatic effect through apoptosis by targeting the JNK/p38 pathway in human nasopharyngeal carcinoma cells. Therefore, licochalcone A is a promising therapeutic agent for the treatment of human nasopharyngeal cancer cells.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high invasive and metastatic properties. Dysregulation of miRNAs may contribute to disease progression by targeting disease-related genes. In this study we aimed to elucidate the role and function of aberrantly expressed miRNA in NPC tumorigenesis. We found that miR-1178-3p was highly expressed in NPC tissues. Overexpression of miR-1178-3p promoted the proliferation, migration and invasion of NPC cells in vitro. In contrast, knocking down endogenous miR-1178-3p by miRNA-specific inhibitor significantly suppressed the above phenotypes. Moreover, miR- 1178-3p was shown to negatively regulate serine/threonine-protein kinase 4 (STK4), an NPC-related tumor suppressor gene, in the post-transcriptional level. Furthermore, STK4 overexpression abolished miR-1178- 3p-induced cell proliferation, migration and invasion through STK4-mediated dephosphorylation of AKT. Our results indicate that miR-1178-3p acts as an oncomiRNA in NPC by suppressing STK4 expression, and inhibition of miR-1178-3p may become a therapeutic potential for NPC.

A unique case of eyelid metastasis from nasopharyngeal chondroid chordoma in a 63-year-old woman was reported. Chordomas are rare tumors of the bone deriving from remnants of the embryonic notochord. Histologically, the tumor showed lobulated structure and concludes two types of cells: liquid drop cell and small round/cubic cell. Immunohistochemically, AE1/AE3, epithelial membrane antigene (EMA), and S100 showed a uniform and strong positivity. It has a great capacity for recurrence and malignant transformation, despite their slow-growing nature. The most common sites of metastases are liver, lungs, and bones. The eyelid metastasis from chordoma is an extremely rare finding, which may suggest a poor prognosis for the patient. Its significant clinicopathological characteristic could prompt us to take it into consideration when assessing the patient's prognosis.

BACKGROUND: This study investigated the impact of post-radiation sinusitis on the prognosis of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT).
METHODS: Two hundred and thirty patients with non-metastatic NPC were analyzed in terms of freedom from local failure (FFLF), freedom from distant failure (FFDF), overall survival (OS), and disease-free survival (DFS). For each patient, the status of the sinus mucosa was flexibly assessed by documenting mucosal changes as indicated by differences between images obtained before radiotherapy and more than 6 months post-radiation.
RESULTS: With a median follow-up of 39.7 months (8 to 81 months), 19 (8.26%) patients relapsed locally, 13 (5.65%) patients failed in the neck, and 26 (11.3%) patients developed distant metastases. The presence of sinusitis noted in images post-radiation was a significant predictor for DFS (p = 0.001), FFLF (p = 0.004), and FFDF (p = 0.015), in addition to having high negative predictive value for local relapse (97.5%).
CONCLUSIONS: This is the first study to investigate the prognostic value of post-radiation sinusitis in NPC patients treated with IMRT. Post-radiation sinusitis was found to be a significant predictor for DFS, FFLF, and FFDF, and was also found to have high negative predictive value for local recurrence (97.5%). It may thus be used as an additional tool for clinicians to determine the possibility of recurrence.

Aims and Methods: Retrospectively, this paper compared the differences of the Epstein-Barr virus (EBV)-encoded small RNAs (EBERs), protein expression and gene mutations of tumor suppressor gene p53 (TP53) in keratinized nasopharyngeal squamous cell carcinoma (KNSCC) and nonKNSCC, and the relationships between pathological features and the prognosis of patients were analyzed.
Results: The positive rate of EBERs hybridization and TP53 expressions was 76.3% and 52.2%, respectively, while the mutation rate of TP53 gene was 39.6%. Logistic regression analysis showed direct relationships between the subtypes of nasopharyngeal squamous cell carcinoma (NPSCC) and EBERs-positive, or frequent consumption of pickled food. Overall survival rates of patients with positive TP53 expression, the TP53 gene mutations, vascular invasions, organ metastases, lymph node metastasis, and clinical recurrence were significantly lower than those of patients without those symptoms. The poorer prognosis was related to regularly drinking and the advanced age. According to the Cox regression analysis, we found that the main prognostic factors of NPSCC patients were the aging, recurrence, TP53 gene mutations, especially exon 7 or 8 mutations.
Conclusions: We concluded that there were the correlations between NPSCC subtypes with EBV infection and frequent intaking of pickled food, while aging, clinical recurrence, and TP53 gene mutations were independent predictors for the poor prognosis of nasopharyngeal carcinoma.

Current treatment of advanced-stage nasopharyngeal carcinoma (NPC) is not satisfactory. Here, we developed a folic acid (FA) modified, gefitinib (GEF) and yttrium 90 (Y90) co-loaded, core-shell structured lipid-polymer hybrid nanoparticles (FA-GEF-Y90-LPNP). The size and zeta potential, drug release behavior, and uptake by tumor cells were investigated. The antitumor efficiency and toxicity of LPNP were evaluated in cancer cells and in tumor bearing mice. FA-GEF-Y90-LPNP with a mean size of 150 nm and zeta potential of -40 mV was able to enhance the accumulation in the NPC cells and exhibited the highest cytotoxicity. The AUC and T

The PPAR coactivator-1α (PGC1α) is an important transcriptional co-activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is rare, but a certain amount of mortality remains in NPC patients. Our study aimed to identify candidate genes as biomarkers for NPC screening, diagnosis, and therapy.
METHODS: We investigated two microarray profile datasets GSE64634 and GSE12452 to screen the potential differentially expressed genes (DEGs) in NPC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were also performed. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. The associated transcriptional factor regulatory network of the DEGs was also constructed.
RESULTS: A total of 152 DEGs were identified from the GSE64634 and GSE12452 datasets, including 10 upregulated and 142 downregulated genes. Gene functional enrichment analysis indicated that these DEGs were enriched in the cilium movement, antimicrobial humoral response, O-glycan processing, mucosal immune response, carbohydrate transmembrane transporter activity, hormone biosynthetic process, neurotransmitter biosynthetic process, and drug metabolism-cytochrome P450 pathway. Five hub genes (DNALI1, RSPH4A, RSPH9, DNAI2, and ALDH3A1) and one significant module (score = 5.6) were obtained from the PPI network. Key transcriptional factors, such as SPI1, SIN3B, and GATA2, were identified with close interactions with these five hub DEGs from the gene-transcriptional factor network.
CONCLUSIONS: With the integrated bioinformatic analysis, numerous DEGs related to NPC were screened, and the hub DEGs we identified may be potential biomarkers for NPC.

BACKGROUND: To identify a radiomics signature to predict local recurrence in patients with non-metastatic T4 nasopharyngeal carcinoma (NPC).
METHODS: A total of 737 patients from Sun Yat-sen University Cancer Center (training cohort: n = 360; internal validation cohort: n = 120) and Wuzhou Red Cross Hospital (external validation cohort: n = 257) underwent feature extraction from the largest axial area of the tumor on pretreatment magnetic resonance imaging scans. Feature selection was based on the prognostic performance and feature stability in the training cohort. Radscores were generated using the Cox proportional hazards regression model with the selected features in the training cohort and then validated in the internal and external validation cohorts. We also constructed a nomogram for predicting local recurrence-free survival (LRFS).
FINDINGS: Eleven features were selected to construct the Radscore, which was significantly associated with LRFS. For the training, internal validation, and external validation cohorts, the Radscore (C-index: 0.741 vs. 0.753 vs. 0.730) outperformed clinical prognostic variables (C-index for primary gross tumor volume: 0.665 vs. 0.672 vs. 0.577; C-index for age: 0.571 vs. 0.629 vs. 0.605) in predicting LRFS. The generated radiomics nomogram, which integrated the Radscore and clinical variables, exhibited a satisfactory prediction performance (C-index: 0.810 vs. 0.807 vs. 0.753). The nomogram-defined high-risk group had a shorter LRFS than did the low-risk group (5-year LRFS: 73.6% vs. 95.3%, P < .001; 79.6% vs 95.8%, P = .006; 85.7% vs 96.7%, P = .005).
INTERPRETATION: The Radscore can reliably predict LRFS in patients with non-metastatic T4 NPC, which might guide individual treatment decisions. FUND: This study was funded by the Health & Medical Collaborative Innovation Project of Guangzhou City, China.

BACKGROUND: Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients.
METHODS: This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival.
RESULTS: Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS.
CONCLUSIONS: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.

AIMS: Our previous study has demonstrated that β-catenin pathway was abnormally activated in nasopharyngeal carcinoma (NPC). The purposes of the present study are to investigate whether the alterations of LEF1 and TCF1 (TCF7) proteins, the important components of the canonical Wnt/β-catenin pathway, are associated with clinicopathological features and prognostic implications.
METHODS: We collected 391 cases of NPC, 53 non-cancerous control nasopharyngeal mucosa and 28 pairs of NPC and their matched metastases, detected expression of LEF1 and TCF1 (TCF7) proteins in these tissues by immunohistochemistry.  RESULTS: Results showed that there were significantly increased expression of both LEF1 and TCF1 (TCF7) proteins and coexpression of LEF1 and TCF1 (TCF7) in NPC than these in non-cancerous nasopharyngeal mucosa (all p<0.001), as well as LEF1 and coexpression of LEF1 and TCF1 (TCF7) in matched metastasis NPCs than these in the primary NPCs (p=0.003 and p=0.014, respectively). In addition, expression of LEF1 and the coexpression of LEF1 and TCF1 (TCF7) proteins were positively correlated with lymph node metastasis (p=0.001 and p=0.020, respectively), advanced clinical stage (p<0.003 and p=0.027, respectively) and poor survival status of patients with NPC (p<0.001 and p=0.004, respectively). Moreover, multivariate Cox regression analysis identified that the positive expression of LEF1 was the independent poor prognostic factor for overall survival of patients with NPC (p<0.001).
CONCLUSIONS: The expression of LEF1 associated positively with TCF1 (TCF7) and clinical progression of NPC, and positive expression of LEF1 protein may act as valuable independent biomarker to predict poor prognosis for patients with NPC.

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer. Distant metastasis becomes the predominant mode of treatment failure in NPC patients. Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from traditional Chinese medicine ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 inhibits the migration and invasion activity of NPC cells and to explore the possible mechanisms. Our results revealed that Rg3 hampers cell migration and invasion in both HNE1 and CNE2 cell lines. A reduced level of matrix metalloproteinase-2 (MMP-2) and MMP-9 was induced by Rg3 treatment. In addition, Rg3 significantly altered the expression of epithelial mesenchymal transition (EMT) markers with increased E-cadherin but decreased Vimentin and N-cadherin expression. Transforming growth factor

BACKGROUND: The purpose/aim of this study was to 1) use magnetic resonance diffusion tensor imaging (DTI), fibre bundle/tract-based spatial statistics (TBSS) and machine learning methods to study changes in the white matter (WM) structure and whole brain WM network in different periods of the nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT), 2) identify the most discriminating WM regions and WM connections as biomarkers of radiation brain injury (RBI), and 3) supplement the understanding of the pathogenesis of RBI, which is useful for early diagnosis in the clinic.
METHODS: A DTI scan was performed in 77 patients and 67 normal controls. A fractional anisotropy map was generated by DTIFit. TBSS was used to find the region where the FA differed between the case and control groups. Each resulting FA value image is registered with each other to create an average FA value skeleton. Each resultant FA skeleton image was connected to feature vectors, and features with significant differences were extracted and classified using a support vector machine (SVM). Next, brain segmentation was performed on each subject's DTI image using automated anatomical labeling (AAL), and deterministic white matter fiber bundle tracking was performed to generate symmetrical brain matrix, select the upper triangular component as a classification feature. Two-sample t-test was used to extract the features with significant differences, then classified by SVM. Finally, we adopted a permutation test and ROC curves to evaluate the reliability of the classifier.
RESULTS: For FA, the accuracy of classification between the 0-6, 6-12 and > 12 months post-RT groups and the control group was 84.5, 83.9 and 74.5%, respectively. In the case groups, the FA with discriminative ability was reduced, mainly in the bilateral cerebellum and bilateral temporal lobe, with prolonged time, the damage was aggravated. For WM connections, the SVM classifier classification recognition rates of the 0-6, 6-12 and > 12 months post-RT groups reached 82.5, 78.4 and 76.3%, respectively. The WM connections with discriminative ability were reduced.
CONCLUSIONS: RBI is a disease involving whole brain WM network anomalies. These brain discriminating WM regions and WM connection modes can supplement the understanding of RBI and be used as biomarkers for the early clinical diagnosis of RBI.

BACKGROUND: Epithelial-mesenchymal transition (EMT) may be one of the reasons for the failure in some clinical trials regarding histone deacetylase inhibitors (HDACIs)-treated solid tumors. We investigated the effects of a pan-HDACI trichostatin A (TSA) on the proliferation and EMT of nasopharyngeal carcinoma (NPC) cells.
METHODS: Poorly-differentiated NPC cell line CNE2 and undifferentiated C666-1 were treated with various concentrations of TSA, the cell viability was assessed by CCK-8 assay, the morphology was photographed, and the mRNA level of HDACs was assessed by semiquantitative PCR. After determination the cell cycle distributions, cells were subjected to western blotting analysis of cell cycle and EMT-associated genes expression. And the changes in migration ability were assessed by transwell migration assay and scratch wound healing assay. Finally, histone deacetylases activator ITSA-1 was used to assess the reverse of TSA-induced changes in NPC cells.
RESULTS: TSA inhibited the proliferation of CNE2 and C666-1 cells in a concentration-dependent manner and arrested the cell cycle at G1 phases. TSA reduced PCNA, cyclin D1, cyclin E1, CDK2, p16 and p21 expressions and stimulated CDK6 levels. TSA stimulation for 48 h could effectively induce the EMT in CNE2 and C666-1 cells, which showed an increase of spindle-like cells and promoted expression of Vimentin and Snail1 expression in a concentration-dependent manner. Surprisingly, this short period of TSA treatment that induced EMT also impeded the migration ability of CNE2 and C666-1 cells. Interestingly, ITSA-1 rescued TSA-impeded CNE2 and C666-1 cells' proliferation, migration and HDACs expression, also re-induced the cells to turn into epithelial cell phenotypes.
CONCLUSIONS: These results indicate that short-term stimulation of TSA effectively inhibits cell proliferation and induce EMT-like changes in NPC cells but not increase its invasion ability.

PURPOSE: Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been deemed an oncogene in many human cancers. However, the underlying mechanism of NEAT1 in nasopharyngeal carcinoma (NPC) progression remains largely unclear.
MATERIALS AND METHODS: Quantitative real-time PCR assay was performed to assess the expression of NEAT1 and miR-34a-5p in NPC tissues and cells. Western blot analysis was used to observe cell epithelial to mesenchymal transition (EMT) and the activation of Wnt/β-catenin signaling in 5-8F cells. MiRNA directly interacting with NEAT1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation. Cell proliferation ability was determined by CCK-8 assay, and cell migration and invasion capacities were assessed by transwell assays. An animal model was used to investigate the regulatory effect of NEAT1 on tumor growth
RESULTS: Our data revealed that NEAT1 is upregulated, while miR-34a-5p is downregulated in NPC tissues and cell lines. NEAT1 knockdown repressed tumor growth
CONCLUSION: Our study demonstrated that NEAT1 targets miR-34a-5p at least partly to drive NPC progression by regulating Wnt/β-catenin signaling, suggesting a potential therapeutic target for NPC.

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aims to investigate the role and mechanism of LINC00520 in the NPC carcinogenesis. Results indicated that LINC00520 was significantly increasing in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00520 indicated the poor prognosis of NPC patients. Silence of LINC00520 was able to repress NPC cell growth in vitro while overexpression of LINC00520 inversed this process. Moreover, in vivo tumor xenografts were establishing using CNE-1/SUNE-1 cells to investigate the function of LINC00520 in NPC tumorigenesis. Rescue assay was conducting to further confirm that LINC00520 contributed to NPC progression by regulating miR-26b-3p/ubiquitin-specific protease 39 (USP39) signal pathway. Taken together, our study discovered the oncogenic role of LINC00520 in clinical specimens and cellular experiments, showing the potential LINC00520/miR-26b-3p/USP39 pathway. This results and findings provide a novel insight for NPC tumorigenesis.

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666‑1, 5‑8F and SUNE‑1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE‑1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell Counting Kit‑8, wound healing and Transwell assays, respectively. KRT6A levels, metastasis‑associated factors and the Wnt/β‑catenin pathway were measured using RT‑qPCR and western blotting. It was demonstrated that KRT6A was upregulated in all detected NPC cells, among which KRT6A was the highest in SUNE‑1 cells. In SUNE‑1 cells, cell viability was inhibited at 24 and 48 h, and that cell metastasis and invasion were demonstrated to be suppressed by KRT6A silencing. Both the mRNA and protein levels of KRT6A, matrix metalloproteinase (MMP)‑2, MMP‑9, β‑catenin, lymphoid enhancer binding factor 1 and T‑cell specific factor 4 were reduced in the small interfering (si)KRT6A group. However, the results demonstrated that the levels of epithelial‑cadherin and tissue inhibitor of metalloproteinase‑2 (TIMP‑2) were promoted in the siKRT6A group. The activation of the Wnt/β‑catenin pathway by lithium chloride reversed the effect of si‑KRT6A by modulating the expression of MMP‑2/9 and TIMP2. It was observed that KRT6A silencing suppressed cell invasion and metastasis of NPC via the β‑catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.